Lecture 4

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Basic Virology
I.
Properties replication and classification of viruses
1. Size and shape
 Size range from 20-300 nm
 Shape : most of viruses are spherical or filamentous or
complex or helical
2. Structure
a. Genome : Viruses contain either DNA or RNA
b. Capsid: a protein coat enclosing the genome and
core protein
c. Envelope : Lipid bilayer membrane surrounding
the capsid of some viruses.
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Virus replication: in host cells involves the following steps
1. Attachment to cell surface molecules (receptors)
2. Penetration of the viruses into the host cell by:
- Endocytosis
- Injection of nucleic acid
- Fusion of envelope with host membrane
3. Replication of viral protein of nucleic acid and attached core
protein in order to direct the host cell ribosome to produce
viral proteins.
4. Assembly and maturation to form viral particles (virions,
empty particles).
5. Release of the virus.
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Bacteriophages
Definition:
Viruses
that
infect
bacteriophages.
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bacteria
are
known
as
Virus classification:
Viruses can be classified according to:
1. Disease or organ system involved
2. Nucleic acid type/virus structure
3. Replication.
Detection of virus infections
1. Direct detection of virus particles, viral antigen, viral lesions
or nucleic acid, by microscope, particle agglutination,
immunoflouresence, serology, PCR or RT-PCR.
2. Indirect detection of virus-specific host response by serology
e.g. complement fixation test , haemagglutionation test ,
ELISA, etc.
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Common viral infection
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I.
RNA viruses
1. Influenza virus
 Common cause of Respiratory tract infection
 Three types A, B and C
 Spread by droplets
 Infection of upper respiratory tract causing; incubation period
1-4 days followed by virus replication upper in upper
respiratory tract.
 Epidemic occurs in types A, B, C but pandemic occurs
mostly in type A.
 Treatment : Amantadine or rimantadine , for prophylaxis
only.
 Prevention: inactivated vaccine (whole virus or subunit given
intramuscularly) have an efficacy of 60-80% .
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2. Mumps
 Transmission: By droplet or contact with saliva.
 Occur in children 5-15 y/o
 Incubation period is 18-21 days. There is a short prodromal
phase (48 hr) of malaise and fever followed by parotid gland
enlargement.
 Complication:
- Meningitis, often mild in < 5% of cases
- Epididymo-orchitis in about 25% of adult males
infected with the virus.
- Pancreatitis, myocarditis, arthritis, oophoritis.
 Prevention: Attenuated live virus vaccine is normally given
in combination with measles and rubella vaccine (MMR) in
childhood immunization schemes.
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3. Measles:
 Transmission by Droplet spread. Highly infectious.
 Incubation period is 9-10 days. There is a prodromal phase
(48 h) of fever, cough , rhinitis and conjunctivitis, followed
by the appearance of a maculopapular rash starting on the
face and trunk, and spreading peripherally; lesion also
present on the mucosa , particularly in the mouth.
 Complication:
- Pneumonia
- Encephalitis
- Otitis media
 Prevention: Attenuated live virus vaccine is normally given
in combination with rubella and mumps vaccine (MMR).
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4. Rubella
 Transmission by Droplets
 Incubation period is 14 days, with primary replication in the
cervical lymph nodes , followed by rash
 Primary infection during the first 12 weeks of pregnancy
often causes generalized fetal infection leading to intrauterine
death /abortion , nerve deafness, cardiac abnormalities,
hepatosplenomegaly
,
jaundice
(congenital
rubella
syndrome). Enlargement of the suboccipital lymph node is a
typical feature.
 Prevention: MMR vaccine
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5. Polio viruses
 Cause poliomyelitis which affect C.N.S.
 Only a minority of polio infection is paralytic. Infection
occurs by:
- Oral route through contaminated food, milk or water,
- Stools of a cases or a carrier.
- House flies play a mechanical role in transmission.
- Respiratory transmission
 After polio virus infection, one of the following pictures may
occur
1. In-apparent infection: in which primary replication of
the virus occurs in the oropharynx and intestinal
mucosa  the virus excreted in the stool or pharyngeal
mucus
2. Abortive poliomyelitis: virus will go to lymph nodes
with subsequent blood invasion may occur. This is
accompanied with fever , malaise and gasterointestinal
manifestation.
3. Paralytic poliomyelitis: when virus reach CNS via
blood stream leading to meningitis and paralysis.
Meningitis may occur without paralysis.
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 Most of infection occur as in-apparent or abortive. Paralytic
poliomyelitis occur in 0.1-1% of cases only.
 Vaccination: Sabin ' living attenuated vaccine
 Living non paralytic strain
 Active immunization of all infants starting when 3 months
old.
 Giving orally : 3 doses are required to ensure multiplication
in gut with both local (IgA in gut)
and serum antibody
production.
6. Rota viruses
 Responsible for 50-60% of acute gastroenteritis in infants
and children between age 6 months- 12 years.
 Infect cells in the villi of the small intestine  disturb
transport mechanisms; impairing sodium and glucose
absorption.
 The damaged cell slough in the lumen of the intestine leading
to release of large quantities of the virus which appears in the
stools.
 Diagnosis based on the demonstration of the virus or its
antigen in the stool of the patient using ELISA /Agglutination
test.
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7. Human immunodeficiency virus (HIV)
 Two types HIV-1 & HIV-2
 Replication:
- Attachment to T lymphocyte (CD4 cells)
- Penetration by endocytosis
- Replicatoin
- Assembly : intracytoplasmic mophogenesis
- Synthesis of DNA by viral reverse transcriptase
- Release of virus particles by budding
 Diagnosis: by detection of HIV-specific antibody by passive
particle agglutination test, ELISA, Western blotting or PCR
 Transmission by infected blood, sexual intercourse or from
mother to child during pregnancy  early impairment of
immune cells specially T cells (CD4)  humoral antibody
response against HIV specific protein develps  in later
stage deficiency of both the humoral and cellular immune
response develops.
 Disease: Acquired immunodeficiency syndrome (AIDS)
characterized by severe disease due to generalized infections
with bacteria, virus, fungi , protozoa and associated with
tumors (Kapposi’s sarcoma, lymphoma)
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 Treatment: Zidovudine (azidothymidine) limited response.
Other anti HIV compounds (dideoxycytidine).
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6. Hepatitis A virus (HAV)
 Transmitted by fecal-oral route. Outbreaks have been
associated with infected food handlers and ingestion of
contaminated shellfish.
 Clinically:
- Incubation period 2-6 weeks followed by malaise,
anorexia, nausea and right upper quadrant pain.
- Jaundice appear during the second week and normally
last several weeks, but may be prolonged.
- Fulminant liver failure occur in rare case. Chronic liver
disease is not a feature of HAV infection.
 Disease: Acute hepatitis. In most cases there is complete
recovery, with specific antibody response persisting lifelong.
There is not carrier state
 Diagnosis:
- Liver function tests show markedly elevated serum
levels of liver enzymes (aminotransferases) and
bilirubin.
- Diagnosis is confirmed by the detection of serum IgM
antibody to HAV.
 Treatment: General bed rest. Vaccine now available.
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7. Hepatitis C virus (HCV).
 HCV is the cause of about 90% of hepatitis.
 Transmission occur in infected blood product, intravenous
drug abuse, ? sexual transmission)
 Clinical features: incubation 2-6 months. The hepatitis is
often mild but frequently progresses to chronic active
hepatitis and cirrhosis after many years (> 25 years), with an
increased risk of developing liver carcinoma.
 Diagnosis: by serology test, antibody to HCV and
polymerase chain reaction (HCV-PCR).
 Prevention: no vaccine available yet.
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II.
DNA viruses
1. Herpes simplex virus (HSV)
 There are two serotypes, HSV 1 & HSV 2.
 Transmission is via virus infected saliva (HSV 1), sexual
contact (HSV 2) or direct contact with vesicles.
 Following primary infection (often asymptomatic), HSV
remains latent in the sensory ganglia, reactivation results in
secondary infection.
 Clinical features:
- Stomatitis: seen in children and immunocompramized
patients.
- Herpes labialis (cold sore): crops of vesicles around
lips; result from reactivation of HSV in response to
various stimuli (e.g. stress, sunlight).
- Central
nervous
system
infection:
meningitis
,
encephalitis
- Genital infection
- Eye infection
- Multisystem infection in the immunocompromized.
 Treatment: Acyclovir is useful for active infection, but does
not eliminate latent HSV.
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2. Hepatitis viruses : Hepatitis B Virus (HBV)
 Major cause of parenterally transmitted hepatitis.
 Virus : DNA virus , consisting of
- Core , DNA circular genome
- Nucleocapsid (hepatitis B core antigen , HBcAg)
- Envelope (Hepatitis B surface , HBsAg)
- (HBeAg) is a cleavage produce of the core found on
infected cells or free in serum.
 Transmission: is by percutaneous and permucosal route, there
are three important mechanism of transmission;
- Contact transmission via bodily secretion (e.g. blood,
semen and vaginal fluid)
- Maternal infant transmission across the placenta or
during delivary.
- Percutaneous transmission: e.g. parenteral drug abuse
and health care workers involved needlestick injuries.
Infection via transfusion of contaminated blood
product.
 Chronic HBsAg carriers have an increased risk in developing
hapatocellular carcinoma.
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 Clinically : an incubation period 6 weeks to 6 months is
followed by malaise, anorexia and jaundice.
 Disease: acute and chronic hepatitis ; hepatocellular
carcinoma.
 Diagnosis: serological tests are made by immunoassay
detecting HBsAg, HBeAg, and antibodies to HBcAg (IgM,
IgG), anti-HBeAg, anti-HBsAg.
 Treatment: corticosteroids and azathioprine are used in
severe cases of chronic but not acute hepatitis. Interferon is
given in cases of chronic active hepatitis.
 Prevention: HBV vaccine. Neonatal vaccination prevent
transmission from carrier mother.
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3. Cytomegalovirus (CMV)
 caused by human cytomegalovirus (HCMV)
 dsDNA virus
 causes formation of intranuclear inclusion bodies and
cytoplasmic inclusions
 virus shed in semen and cervical solutions
 can also be transmitted by blood transfusions and organ
transplants
 usually asymptomatic infection with viremia.
 Infection of the neonate may be azquired in utero. 10% of
infected infants are symptomatic at birth, showing lethargy,
jaundice,
convulsions,
thrombocytopenia,
hepatosplenomegaly. 60% of infants born to infected mothers
acquire the disease by breast milk during perinatal period.
 > 90% of surviving infected infants develop complications
later in life that include mental retardation, hearing loss and
learning disabilities.
 can be serious in immunocompromised individuals
 symptoms often resemble mononucleosis
 treatment, prevention, and control
 antiviral agents (Gancyclovir) used for high-risk patients
 avoiding close personal contact with actively infected
individual
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